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Muscle Performance
This page focuses on muscle perfomrance from the perspective of slow-twitch (type I) and fast-twitch (type II) skeletal muscle fibers. Of particular interest here is the performance of fast-twitch muscles as determined by the expression of different alleles of the gene ACTN3. Muscle Muscle is composed of 2 classes of muscle fiber; slow-twitch and fast-twitch fibers. Slow-twitch fibers have a slow contraction and contain more myoglobin, used in muscles for oxygen transport. Fast-twitch muscles have a fast contraction and can be subdivided into fibres that produce energy aerobically (type IIa) and anaerobically (type IIb) (1 ). Slow-twitch muscle is believed to be used for endurance purposes (such as long-distance running) whereas fast-twitch muscle is believed to be used for power purposes (such as sprinting or weight lifting). Muscle fibers contain two major proteins, actin and mysoin, which are involved in the contraction of the muscle. Another protein, called actinin , also plays a role in muscle contraction through the binding of actin. The actinin isoform alpha-actinin-3 is found almost exclusively in fast-twitch muscles (specifically type IIb) (2 ). Expression of this protein could relate to the performance of the fast-twitch muscle fibers. ''ACTN3'' and alpha-actinin-3 The gene ACTN3 encodes the protein alpha-actinin-3, an actin binding protein involved in muscle contraction (2 ). In humans, ACTN3 is located on chromosome 11 and is the site of a relatively common single nucleotide polymorphism (a nucleotide change from C to T), which results in a stop codon. The stop codon (X) replaces the amino acid arginine ® at residue number 577 in the protein (R577X). About 18% of the populatino is homozygous for this polymorphism (two stop codons, XX, rather than two arginines, RR, or heterzygous, RX) and do not make any alpha-actinin-3 protein (2 , 3 , 4 , 5 ). This homozygous genotype does not result in a disease phenotype, though it does appear to play a role in the distribution of muscle fiber types (5 ). Athletic Performance Since ther eis no disease phenotype from homozygous R577X conversions, several studies have been conducted to investigate the effect of this polymorphism on athletic performance. These studies have shown an association between a homozygous genotype for alpha-actinin-3 (RR) and an increase in power muscle performance, such as that seen in sprinters and weight lifters. A homozygous genotype for the polymorphism (XX) has been shown to be associated with endurance muscle performance, such as long-distance running. A heterozygous genotype appears to fall into the power performance category, rather than endurance (6 , 7 ). 23andMe 23andMe , a comercial personal genotyping service, uses the a marker for the ACTN3 polymorphism in it's array of single polymorphism markers. Dr. John Burke, who has used this service to discover his genotype, is shown to be heterozygous for this polymorphism (RX, or when looking at the genotype, CT). Based on the published literature concerning this gene and polymorphism, and the fact that John has one working copy of the ACTN3 gene, 23andMe has categorized John in the same pool as many world-class sprinters. References 1. Zierath, J and Hawley, J. Skeletal Muschle Fiber Type: Influence on Contractile and Metabolic Properties. PLoS Biol. (2004) 2. MacArthur, D and North, K. A gene for speed? The evolution and function of alpha-actinin-3. BioEssays. (2004) 3. North, K, et al. A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nature Genetics. (1999) 4. Beggs, A, et al. Cloning and Characterization of Two Human Skeletal Muscle alpha-Actinin Genes Located on Chromosomes 1 and 11. Journal of Biol. Chem. (1992) 5. Vincent, B, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol. Genomics (2007) 6. Papadimitriou, I, et al. The ACTN3 Gene in Elite Greek Track and Filed Athletes. Int. J. Sports Med. (2008) 7. Yang, N, et al. ACTN3 Genotype Is Associated with Human Elite Athletic Performance. Am. J. Hum. Genet. (2003)